Association of Genome-Wide Polygenic Scores for Multiple Psychiatric and Common Traits in Preadolescent Youths at Risk of Suicide

Abstract

IMPORTANCE Suicide is the second leading cause of death among youths worldwide, but no available means exist to identify the risk of suicide in this population.OBJECTIVE To assess whether genome-wide polygenic scores for psychiatric and common traits are associated with the risk of suicide among preadolescent children and to investigate whether and to what extent the interaction between early life stress (a major environmental risk factor) and polygenic factors is associated with suicidal thoughts and behaviors among youths. DESIGN, SETTING, AND PARTICIPANTSThis cohort study analyzed the genotype-phenotype data of 11 869 preadolescent children aged 9 to 10 years from the Adolescent Brain and Cognitive

Genetic risk, parental history, and suicide attempts in a diverse sample of US adolescents

“…This disparity is especially concerning in the field of youth suicide, where Black US youth are particularly vulnerable (2,17). Our findings extend recent ABCD Study results showing associations of depression polygenic risk score with suicide attempt in an analysis limited to European ancestry (18) and schizophrenia polygenic risk score with suicide attempt reported in the baseline ABCD Study assessment in admixed population with substantially fewer suicide attempt participants (64 versus 182 in the current analysis) (19).…”

Genetics and epigenetics of self‐injurious thoughts and behaviors: Systematic review of the suicide literature and methodological considerations

“…PRS for psychiatric disorders including MDD, BD, schizophrenia (SCZ), attention‐deficit/hyperactivity disorder (ADHD), autism, cannabis use, post‐traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), and anxiety have all been associated with SITB outcomes. The highest percentage variance explained for a psychiatric PRS was for SCZ, explaining up to 11.8% of variability in child SA (Joo et al, 2022).…”

“…An emerging body of work is deploying polygenic scores derived from adult GWAS samples in youth datasets (Daskalakis et al, 2021; Joo et al, 2022; Lee et al, 2021), as currently there are no large GWAS of SITB based in youth samples. These studies have identified significant associations between adult GWAS‐derived PRS for various traits and child SITB.…”

“…There is therefore potential in the literature for studies aiming to validate PRS of adult SITB in youth populations to determine if they explain a similar amount of variability in the youth SITB phenotypic outcomes. An interesting body of work is emerging testing adult‐based polygenic scores in child samples (Daskalakis et al, 2021; Joo et al, 2022; Lee et al, 2021); these studies have generally shown that adult‐based polygenic scores for complex traits such as psychiatric disorders do predict SITB outcomes in childhood, albeit weakly. However, none of these studies so far have tested polygenic scores for SITB and explained variance in children.…”

“…An emerging body of work is deploying polygenic scores derived from adult GWAS samples in youth datasets (Daskalakis et al, 2021;Joo et al, 2022;Lee et al, 2021) In addition, aside from psychiatric disorders, a multigenic score built with 750 neurodevelopmental genes explained 4.9% of variance in SA for Europeans (Sokolowski et al, 2016a), while a three-locus score for HTR2A, TPH1 and TPH2 explained 5% of variance in SA for Europeans (Pompili et al, 2017), and a four-locus score across FKBP5, RORA, CHRNA5, and CRHR1 predicted SA or suicide plan in a largely European sample (Boscarino et al, 2022).…”